Backgroud: This study aimed to determine the effects of early antibiotic intervention (EAI) on subsequent blood parameters, apparent nutrient digestibility, and fecal fermentation profile in pigs with different dietary crude protein (CP) levels. Eighteen litters of piglets (total 212) were randomly allocated to 2 groups and were fed a creep feed diet with or without in-feed antibiotics (olaquindox, oxytetracycline calcium and kitasamycin) from postnatal d 7 to d 42. On d 42, the piglets within the control or antibiotic group were mixed, respectively, and then further randomly assigned to a normal- ( Results: EAI increased (P < 0.05) albumin and glucose concentrations in low-CP diet on d 77, and increased (P < 0.05) urea concentration in normal-CP diet. On d 185, EAI increased (P < 0.05) globulin concentration in normal-CP diets, but decreased glucose concentration. For nutrient digestibility, EAI increased (P < 0.05) digestibility of CP on d 77. For fecal microbiota, the EAI as well as low-CP diet decreased (P < 0.05) E. coli count on d 77. For fecal metabolites, on d 77, EAI decreased (P < 0.05) total amines concentration but increased skatole concentration in low-CP diet. On d 185, the EAI increased (P < 0.05) putrescine and total amines concentrations in low-CP diets but reduced (P < 0.05) in the normal-CP diets. The low-CP diet decreased the concentrations of these compounds. Conclusions: Collectively, these results indicate that EAI has short-term effects on the blood parameters and fecal microbial fermentation profile. The effects of EAI varied between CP levels, which was characterized by the significant alteration of glucose and putrescine concentration.

In-feed antibiotics have been used to promote growth in piglets, but its impact on metabolomics profiles associated with host metabolism is largely unknown. In this study, to test the hypothesis that antibiotic treatment may affect metabolite composition both in the gut and host biofluids, metabolomics profiles were analyzed in antibiotic-treated piglets. Piglets were fed a corn-soy basal diet with or without in-feed antibiotics from postnatal day 7 to day 42. The serum biochemical parameters, metabolomics profiles of the serum, urine, and jejunal digesta, and indicators of microbial metabolism (short-chain fatty acids and biogenic amines) were analyzed. Compared to the control group, antibiotics treatment did not have significant effects on serum biochemical parameters except that it increased (P < 0.05) the concentration of urea. Antibiotics treatment increased the relative concentrations of metabolites involved in amino-acid metabolism in the serum, while decreased the relative concentrations of most amino acids in the jejunal content. Antibiotics reduced urinary 2-ketoisocaproate and hippurate. Furthermore, antibiotics decreased (P < 0.05) the concentrations of propionate and butyrate in the feces. Antibiotics significantly affected the concentrations of biogenic amines, which are derived from microbial amino-acid metabolism. The three major amines, putrescine, cadaverine, and spermidine, were all increased (P < 0.05) in the large intestine of antibiotics-treated piglets. These results identified the phenomena that in-feed antibiotics may have significant impact on the metabolomic markers of amino-acid metabolism in piglets.

In-feed antibiotics have been commonly used to promote the growth performance of piglets. The antibiotics can increase protein utilization, but the underlying mechanism is largely unknown. The present study investigated the effects of in-feed antibiotics on intestinal AA transporters and receptors to test the hypothesis that the alteration of circulating AA profiles may be concomitant with the change of intestinal AA transporters and receptors. Sixteen litters of piglets at day 7 started to receive creep feed with (Antibiotic) or without (Control) antibiotic. Piglets were weaned at day 23 after birth, and fed the same diets until day 42. In-feed antibiotics did not affect the BW of 23-day-old (P = 0.248), or 42-day-old piglets (P = 0.089), but increased the weight gain to feed ratio from day 23 to 42 (P = 0.020). At day 42 after birth, antibiotic treatment increased the concentrations of most AAs in serum (P < 0.05), and decreased the concentrations of most AAs in jejunal and ileal digesta. Antibiotics upregulated (P < 0.05) the mRNA expression levels for jejunal AAs transporters (CAT1, EAAC1, ASCT2, yLAT1), peptide transporters (PepT1), and Na-K-ATPase (ATP1A1), and ileal AA transporters (ASCT2, yLAT1, bAT, and BAT1), and ATP1A1. The antibiotics also upregulated the mRNA expression of jejunal AAs receptors T1R3 and CaSR, and ileal T1R3. Protein expression levels for jejunal AA transporters (EAAC1, bAT, and ASCT2) and PepT1 were also upregulated. Correlation analysis revealed that the alterations of AA profiles in serum after the in-feed antibiotics were correlated with the upregulations of mRNA expression levels for key AA transporters and receptors in the small intestine. In conclusion, the in-feed antibiotics increased serum level of most AAs and decreased most AAs in the small intestine. These changes correlated with the upregulations of mRNA expression levels for key AA transporters and receptors in the small intestine. The findings provide further insights into the mechanism of in-feed antibiotics, which may provide new framework for designing alternatives to antibiotics in animal feed in the future.

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The study aimed to evaluate the effects of early antibiotic intervention (EAI) on bacterial fermentation patterns and mucosal immune markers in the colon of pigs with different protein level diets. Eighteen litters of piglets at day (d) 7 were fed creep feed without or with growth promoting antibiotics until d 42. At d 42, pigs within each group were further randomly assigned to a normal- or low-crude protein (CP) diet. At d 77 and d 120, five pigs per group were slaughtered for analyzing colonic bacteria, metabolites, and mucosal gene expressions. Results showed that low-CP diet increased propionate and butyrate concentrations at d 77 but reduced ammonia and phenol concentrations (P < 0.05). EAI increased p-cresol and indole concentrations under normal-CP diet at d 77 (P < 0.05). Low-CP diet significantly affected (P < 0.05) some bacteria groups (Firmicutes, Clostridium cluster IV, Clostridium cluster XIVa, Escherichia coli, and Lactobacillus), but EAI showed limited effects. Low-CP diet down-regulated gene expressions of pro-inflammatory cytokines, toll-like receptor (TLR4), myeloid differentiating factor 88 (MyD88), and nuclear factor-κB p65 (NF-κB p65) (P < 0.05). EAI up-regulated mRNA expressions of interleukin-8 (IL-8) and interferon-γ (IFN-γ) under normal-CP diet at d 77 (P < 0.05). Furthermore, reductions of E. coli and ammonia under low-CP diet were positively correlated with down-regulated gene expressions of pro-inflammatory cytokines, which were positively correlated with the down-regulated TLR4-MyD88-NF-κB signaling pathway. In conclusion, EAI had short-term effects under normal-CP diet with increased aromatic amino acid fermentation and gene expressions of pro-inflammatory cytokines. Low-CP diet markedly reduced protein fermentation, modified microbial communities, and down-regulated gene expressions of pro-inflammatory cytokines possibly via down-regulating TLR4-MyD88-NF-κB signaling pathway.

BackgroundCompared with oral antibiotics (primarily disrupt foregut microbiota), the present study used antibiotics with ileum terminal infusion to disrupt the hindgut microbiota, and investigated the changes in specific bacterial composition and immune indexes in the jejunum and colon, and serum of growing pigs. Twelve barrows (45 d of age, 12.08 ± 0.28 kg) fitted with a T-cannula at the terminal ileum, were randomly assigned to two groups and infused either saline without antibiotics (Control) or with antibiotics (Antibiotic) at the terminal ileum. After 25 d experiment, all pigs were euthanized for analyzing bacterial composition and immune status.ResultsIleum terminal antibiotic infusion (ITAI) altered dominant bacteria counts, with a decrease in Bifidobacterium, Clostridium cluster IV and Clostridium cluster IV in the colon (P < 0.05), and an increase in Escherichia coli in the jejunum (P < 0.05). ITAI decreased (P < 0.05) short-chain fatty acids concentrations in the colon. ITAI decreased interleukin-8 (IL-8), IL-10 and secretory immunoglobulin A (sIgA) concentrations, and down-regulated IL-10, Mucin-1 (MUC1), Mucin-2 (MUC2) and zonula occludens-1 (ZO-1) mRNA expression in the colonic mucosa (P < 0.05). In the jejunal mucosa, ITAI decreased interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), sIgA and IgG levels together with down-regulation of IFN-γ, TNF-α, MUC2 and ZO-1 mRNA expression (P < 0.05). Furthermore, ITAI decreased IL-10, INF-γ, TNF-α, IgA and IgG concentrations in serum (P < 0.05). Correlation analysis revealed that the change in intestinal microbiota was correlated with alterations of Ig and cytokines.ConclusionsITAI affected jejunal and colonic specific bacteria counts, and altered some immune markers levels in the jejunal and colonic mucosa and serum. These findings implicate the potential contribution of hindgut bacteria to immune response in the intestinal mucosa and serum of growing pigs.Electronic supplementary materialThe online version of this article (10.1186/s40104-018-0265-x) contains supplementary material, which is available to authorized users.

BACKGROUND: This study evaluated the effects of early antibiotic exposure (EAE) on subsequent amino acid (AA) profiles and small intestinal AA transporter and receptor expression level in pigs with different dietary crude protein (CP) levels. Eighteen litters of piglets were fed creep feed diets, either with or without antibiotics while with sow on day 7. The pigs were weaned at day 23 and fed the same diets until day 42, when random pigs within each group were offered a normal-or low-CP diet, thereby creating four groups. On day 120, the pigs were euthanized, and jejunal and ileal mucosa and digesta were collected for gene-expression and AA-concentration analysis. RESULTS: With the normal-CP diet, EAE increased (P < 0.05) the concentrations of six essential amino acids (EAA) and three non-essential amino acids (NEAA) in serum, four EAAs and four NEAAs in jejunal mucosa, one EAA and two NEAAs in ileal mucosa, five EAAs and three NEAAs in jejunal digesta, and three EAAs and two NEAAs in ileal digesta. Early antibiotic exposure upregulated (P < 0.05) CAT1, ASCT2, ATB 0,+ , CaSR, T1R1, and T1R3 expression in the jejunum, downregulated PepT1 expression with a normal-CP diet. It upregulated (P < 0.05) the expressions of CAT1, ATB 0,+ , ATP1A1, and T1R3 in the ileum with a normal-CP diet.CONCLUSION: These results suggest that EAE has long-term effects on AA profiles, mainly in the jejunum and serum, by increasing AA transporter expression in the intestine, and that these effects may be influenced by dietary CP levels.